The data for this study were taken from the FANTASIIA Registry (Spanish acronym for Atrial fibrillation: Influence of anticoagulation level and type on stroke and bleeding event incidence), a prospective, observational, national, multicenter study that is collecting general information on the current situation and characteristics of the Spanish population with any type of NVAF, following the European AF guideline criteria.1 The main aim of the registry is to evaluate the incidence of thromboembolic and bleeding events in an unselected population of patients with NVAF over 3 years, specifically with reference to the use and type of antithrombotic agent, vitamin K antagonist (VKA) and direct OAC, as well as anticoagulation adjustment (in patients receiving VKA). The FANTASIIA Registry is designed as an initial enrolment visit and 3 follow-up visits at 1, 2, and 3 years. The patients’ clinical and laboratory data are being collected in an electronic case report form.

In our study, we analyzed a cross-sectional baseline data set from the FANTASIIA enrolment visit, focusing on the secondary endpoints of the registry, which concern the general characteristics of NVAF management, initial AF control strategy, rhythm or rate control, treatment type, antiarrhythmic class, and nonpharmacological treatment.

In this preliminary analysis, we studied 1318 consecutive patients, seen at 50 outpatient clinics, with a diagnosis of NVAF (excluding patients with rheumatic mitral valve disease or valvular prostheses), entered in the FANTASIIA Registry by 81 investigators (81% cardiologists, 11% primary care physicians, and 8% internists) between June 2013 and March 2014. The clinics were randomly selected, and located throughout Spain. Inclusion criteria were patients older than 18 years who had been receiving anticoagulant therapy (80% VKA and 20% direct OAC, ie, dabigatran, rivaroxaban or apixaban) for at least 6 months before enrolment. The patients were managed according to routine clinical practice. The FANTASIIA Registry complies with all the principles of the Declaration of Helsinki and the study protocol was approved by the Clinical Research Ethics Committee at Hospital Universitario de Alicante and by all the local ethics committees. All study participants signed the informed consent.

Quantitative variables were described using the mean ± standard deviation or median [interquartile range], depending on whether they followed a normal distribution, which we tested with the Kolmogorov-Smirnov method. For between-group comparisons, we used the Student t test for continuous variables and the chi-square test for qualitative variables. Statistical significance was defined as P<.05. Statistical analyses were performed with SPSS statistical package version 12.

We enrolled 1318 patients throughout Spain who met the aforementioned inclusion and exclusion criteria between June 2013 and March 2014. Baseline characteristics are shown in Table 1. Mean age was 73.8 years (± 9.4 years) and 758 patients (57.5%) were men. The most prevalent risk factor was hypertension, which was observed in 1068 patients (81.0%), followed by hypercholesterolemia in 711 (54.0%), and diabetes mellitus in 386 (29.0%). Other notable comorbidities were ischemic stroke, in 210 patients (15.9%), and major bleeding, in 44 (3.3%). At the initiation visit, most patients, n=948 (71.9%), were treated with acenocoumarol, 68 (5.2%) with warfarin, and 303 (23.0%) with a novel direct OAC. Left atrial appendage closure had been performed in 3 patients (0.2%). Mean scores for thromboembolic and bleeding risk indices were: CHADS2, 2.32; CHA2DS2-VASc, 3.79, and HAS-BLED, 1.99. CHA2DS2-VASc=0 was found in 4.9% of the patients; CHA2DS2-VASc=1 in 24.1%, and CHA2DS2-VASc ≥ 2 in 71% of the patients. HAS-BLED score was < 3 and ≥ 3 in 72.4% and 27.6% of the patients, respectively. Antiplatelets were used in 126 patients (9.8%), aspirin in 95 (7.4%), clopidogrel in 21 (1.6%), prasugrel in 1 (0.1%), and dual antiplatelet therapy was used in 9 patients (0.8%).

Atrial fibrillation was paroxysmal in 367 patients (28%), permanent in 656 (50%), persistent in 231 (17.6%) and long-standing persistent in 59 (4.5%). New-onset AF was found in 66 patients (5%). Time since AF diagnosis was 3.2 years (1.8 years). Nearly a third of the patients (32.2%) were in sinus rhythm at the baseline visit. A rhythm control strategy was chosen in 39.4% of the patients (45.3% of the patients younger than 75 years and 30.2% aged 75 years or older). A rate control strategy was chosen in 60.6% (54.7% younger than 75 years and 69.8% aged 75 years or older) (P < .001). Cardioversion had been performed previously in 41.9% (electrical cardioversion in 19%, pharmacological cardioversion in 22.9%). Ablation had been performed previously in 3.4% (2.2% for paroxysmal AF, 1.3% for persistent AF, and 0.15% for long-standing persistent AF). Table 2 shows the characteristics of patients classified by rhythm or rate control strategy. Patients who received rhythm control were younger, had a lower prevalence of diabetes mellitus, chronic obstructive pulmonary disease, renal impairment and HF, and a higher prevalence of thyroid dysfunction history. The modified Charlson comorbidity index was lower in this group. Rhythm control was chosen in 44.1% of the patients seen by cardiologists and in 19.2% seen by internists or primary care physicians (P<.001). There were no significant differences for the other variables analyzed (Table 2).

Antiarrhythmic agents were only used in 24.7% of patients. The drugs most frequently used for heart rhythm control were amiodarone (12.6%), flecainide (8.9%), propafenone (0.4%), sotalol (0.5%), and dronedarone (2.3%). The drugs most commonly used for heart rate control were beta-blockers (60.2%), digoxin (19.5%), and calcium channel antagonists (verapamil or diltiazem) (10.7%). Table 3 shows the number of patients receiving each drug alone and in combination, in the whole group and by rhythm and rate subgroups. No patients received a combination of 2 or more Class I or III antiarrhythmic agents, while 13.9% received a combination of 2 or more rate-slowing drugs (6.5%) or an antiarrhythmic plus a rate-slowing drug (7.4%). The most common combinations were an antiarrhythmic plus beta-blocker, and beta-blocker plus digoxin (Table 3). Antiarrhythmic agents were more common in the rhythm control group (55.9% vs just 4.5% in the rate control group; P<.001), and rate-slowing drugs were more common in the rate control group (92.4% vs 68.5% in the rhythm control group; P<.001). The combination of antiarrhythmic and rate-slowing drugs was more common in the rhythm control group (15.4% vs 0.7% in the rate control group, P<.001), and the combination of different rate-slowing drugs was more common in the rate control group (10.4% vs 2.9% in the rhythm control group; P<.001) (Table 3).

We also observed differences in the type of drugs used according to left ventricular ejection fraction (LVEF) function. The LVEF was<45% in 206 patients (15.6% of the total) and ≥ 45% in the remaining 1112 patients (84.4%). The rhythm control strategy was less common among patients with reduced LVEF (29.1% vs 41.4%; P<.001). The rate control strategy was more common in both groups, with a marked difference in the reduced LVEF group (70.9% vs 58.6%; P<.001). Table 4 shows the distribution of antiarrhythmic agents by LVEF function. Among patients with reduced LVEF, the use of class III antiarrhythmics was more common than class Ic antiarrhythmics (15.5% vs 0.5%). Beta-blockers were the most commonly used rate-slowing drug in both groups. Digoxin was the most frequently used drug in patients with reduced LVEF function.

Table 5 shows the characteristics and management of patients seen by cardiologists (1066 patients [80.8%]) and internists or primary care physicians (252 [19.2%]). There were no relevant between-group differences in most patient characteristics, except for older age, a higher prevalence of diabetes mellitus and renal impairment, and a slightly higher modified Charlson comorbidity index in patients seen by cardiologists. The prevalence of other cardiovascular risk factors, comorbidities and associated heart diseases (including coronary disease and HF) was similar in both groups (Table 5). As mentioned earlier, rhythm control strategy was significantly less common among patients seen by internists or primary care physicians. Cardiologists used more antiarrhythmic agents (class Ic and III alike), while internists and primary care physicians used more rate control drugs (Table 5). We observed differences in the type of rate-slower drug used: cardiologists used beta-blockers much more, and internists and primary care physicians used digoxin more.

This study is a preliminary analysis of the baseline data in the FANTASIIA Registry, which is still underway. We need to wait until registry closure, scheduled for 2016, to perform a more detailed and appropriate analysis of the management, strategies and antiarrhythmic agents used for NVAF in Spain, because these variables will change over time, according to the clinical course of each patient. Another limitation is that by design, this study analyses drug treatment at the time of the enrollment visit, and does not include drug history or changes.